Safety and Efficacy of Reperfusion Therapies for Acute Ischemic Stroke Patients with Active Malignancy

doi:10.1016/j.jstrokecerebrovasdis.2019.05.018

Journal of Stroke and Cerebrovascular Diseases

Volume 28, Issue 8, August 2019, Pages 2287-2291

https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.05.018 Get rights and content

Abstract

Background and Purpose: Epidemiological correlations between active malignancy (AM) and acute ischemic stroke (AIS) are well-established. However, the effect of reperfusion strategies, particularly mechanical thrombectomy (MT), has been barely investigated in patients with AIS and AM. We aim to evaluate safety and efficacy of reperfusion strategies in such patients. Materials and Methods: We performed a case-control analysis comparing patients with AM and AIS (AM group) to a group of cancer-free patients with AIS (control group). All enrolled patients underwent reperfusion therapies (i.e. intravenous thrombolysis, MT, intravenous thrombolysis plus MT). Main outcomes were 3-month functional independence, successful reperfusion, 3-month mortality, symptomatic intracranial hemorrhage. Results: Total 24 patients with AM and AIS (mean age: 69 ± 10.1) were individually matched to 24 control patients (mean age: 70.7 ± 9.3). In both groups 50% were treated with MT, 46% with intravenous thrombolysis and 4% with intravenous thrombolysis plus MT. No difference were found in successful reperfusion, 3-month functional independence, symptomatic intracranial hemorrhage, and mortality. However an overall mortality of 33% in the AM group was reported. Conclusions: Reperfusion strategies for AIS patients with AM seem to be safe and effective. However an individualized approach to understand cancer stage and life-expectation is warranted.

Introduction

Active malignancy (AM: i.e. malignant cancer, metastasis, current chemo, or radiotherapy) is a well-known risk factor for ischemic stroke.¹ Cancer-related hypercoagulability has been shown to be the most likely factor leading to this cascade.² AM and ischemic stroke are associated to an increased risk of short-term mortality compared to stroke without AM.³ For this reason, stroke physicians often face with the ethical matter of managing such patients in the acute phase of ischemic stroke when intravenous thrombolysis (IVT) and/or, mechanical thrombectomy (MT), or combined IVT and MT (IVMT) must be considered and information about details regarding AM should be obtained. Safety concerns could increase uncertainty, making clinical decision even more challenging. Small series investigating the effects of IVT in patients with acute ischemic stroke (AIS) and AM have shown poor efficacy and safety outcomes with high rate of hemorrhagic transformation.⁴ Despite benefit exceeds costs deriving from the worldwide spread of MT, previous studies have not included patients with chronic diseases affecting life-expectancy.5, 6

Our aim was to test the efficacy and safety of reperfusion strategies (IVT, MT, and IVMT) among AIS patients with AM.

Section snippets

Material and Methods

We performed a retrospective matched cohort study using our prospective local stroke treatment registry between January 2011 and March 2018. Each AM patient with AIS was individually matched to a cancer-free control patient with AIS by the following variables: age, sex, cardiovascular risk factors (hypertension, diabetes, atrial fibrillation, smoking), glycemia, and blood pressure (systolic and diastolic), prestroke modified Rankin Scale (mRS), clinical severity measured by National Institute

Results

Out of 1243 patients undergoing one of the above mentioned reperfusion strategies, 24 AM patients with AIS in the anterior circulation were found and matched with a control group of 24 AIS patients without history of cancer treated with one of the above mentioned reperfusion therapies. Clinical characteristics of AM group are shown in Table 1. In this group, 41.6% of patients had advanced malignancy (stage IV) and the most frequent type of cancer was lung, followed by colorectal, breast and

Discussion

AM may affect short-term survival and represents a challenging ethical matter for stroke physicians. In these patients AIS treatment could result in therapeutic obstinacy if neurological improvement cannot overwhelm quickly worsening of cancer disease. On the other side decision for no AIS treatment could result in a shortening of life-expectancy.

Few studies have investigated outcomes of cancer-related stroke patients after reperfusion strategies. In one of these recanalization after

Conclusions

Our study suggest that reperfusion strategies such as IVT, MT, and IVMT are safe and effective for AIS patients with AM but an individualized screening for life-expectancy seems warranted (Table 4).

Acknowledgments: We thank all stroke neurologists at the comprehensive stroke center of university of Tor Vergata (Angela Giordano MD, Vittoria Carla D'Agostino PhD, Marta Panella MD, Barbara Rizzato PhD, Simone Napolitano MD, Domenico Samà PhD, Francesco Mori, MD) for collection of data.

Authorship Conformation

All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version.

This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue.

Conflict of Interest

The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript.

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Cited by (20)

Efficacy of mechanical thrombectomy in patients with ischemic stroke and cancer
2021, Journal of Clinical Neuroscience
Citation Excerpt :
We found no significant differences in terms of reperfusion rates between patients with and without active cancer. Reports on this topic in literature are controversial and studies describe unaltered [7] or reduced reperfusion rates in cancer patients compared with controls [3]. Among patients with cryptogenic stroke, the successful reperfusion rate in cancer patients, was lower (2/4) compared with non-oncologic patients (37/50), although the low number of cases do not permit to draw any conclusions.
Cancer-related coagulopathy is a known cause of stroke and can lead to formation of thrombi with a unique composition. The effectiveness of mechanical thrombectomy in cancer patients is still unknown. The aim of the study was to evaluate the rate of successful reperfusion and the clinical outcome in cancer patients with stroke treated with endovascular therapies, compared to patients without cancer. We performed a retrospective analysis of consecutive patients with ischemic stroke treated with endovascular therapies at our hospital between January 2008 and January 2016. A sub-group analysis was performed including only patients with cryptogenic stroke. We included in the final analysis 14 patients with active cancer and 267 patients without cancer. Successful reperfusion was achieved in 79% of patients without cancer, and 71% of patients with active cancer (P = 0.68). Patients with cryptogenic stroke and active cancer had a lower reperfusion rate compared to patients with cryptogenic stroke without active cancer, although not significantly so (2/4 cancer patients, 50% vs 37/50, 74%, p: 0.31). Mortality rate was higher among cancer patients. Hemorrhagic transformation occurred in similar proportions in the two groups. Endovascular treatment in cancer patients seems, thus, effective.
Reperfusion Therapy in Acute Ischemic Stroke with Active Cancer: A Meta-Analysis Aided by Machine Learning
2021, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
However, the efficacy and safety of reperfusion therapy in patients with AC are still not established since they have been frequently excluded from clinical trials owing to bleeding concerns, premorbid functional status, and life expectancy.9,10 Although several case studies and observational studies have reported the safety and efficacy of reperfusion therapy for patients with AC,11–14 the results have been inconclusive due to the small number of participants and the heterogeneity of subjects and study designs. Therefore, we aimed to investigate the outcomes and safety of reperfusion therapy according to treatment modality in patients with acute stroke and AC through a systematic review and meta-analysis.
While the prevalence of active cancer patients experiencing acute stroke is increasing, the effects of active cancer on reperfusion therapy outcomes are inconclusive. Thus, we aimed to compare the safety and outcomes of reperfusion therapy in acute stroke patients with and without active cancer.
A comprehensive literature search was conducted for studies comparing the effects of intravenous thrombolysis (IVT) or endovascular treatment (EVT) in ischemic stroke patients with and without active cancer. The literature was screened using both a manual and machine learning algorithm approach. The outcomes evaluated were symptomatic intracerebral hemorrhage (sICH), all-type intracerebral hemorrhage (aICH), successful recanalization, favorable outcomes (modified Rankin Scale, 0–2), and mortality. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) using the random-effects model from the included studies.
Seven studies were analyzed in this meta-analysis. IVT (n = 1012) was associated with an increased risk of sICH (OR, 9.80; 95% CI, 3.19–30.13) in the active cancer group. However, no significant differences in aICH, favorable outcomes, and mortality were found between groups. Although sICH and successful recanalization in the EVT group (n = 2496) were similar, we observed fewer favorable outcomes (OR, 0.55; 95% CI, 0.33–0.93) and a high prevalence of mortality (OR, 2.91; 95% CI, 1.89–4.47) in the active cancer group.
Reperfusion therapy may benefit selected patients with acute ischemic stroke with active cancer, considering the comparable clinical outcomes of IVT and procedure-related outcomes of EVT. These results should be cautiously interpreted and confirmed in future well-designed large-scale studies.
Malignancy-associated ischemic stroke: Implications for diagnostic and therapeutic workup
2024, CNS Neuroscience and Therapeutics
Long-term outcomes of mechanical thrombectomy in acute ischaemic stroke patients with concomitant malignancy
2024, Postepy w Kardiologii Interwencyjnej
A risk model for prediction of diagnosis of cancer after ischemic stroke
2023, Scientific Reports
Systemic thrombolysis in patients with acute stroke and active cancer: a systematic review and meta-analysis
2023, Internal and Emergency Medicine

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: Financial Disclosure: This work was supported by a grant of the Italian Ministry of Health (RF-2013-02358679) to F.S. and G.K.

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Safety and Efficacy of Reperfusion Therapies for Acute Ischemic Stroke Patients with Active Malignancy

Abstract

Introduction

Section snippets

Material and Methods

Results

Discussion

Conclusions

Authorship Conformation

Conflict of Interest

Lancet

Association between incident cancer and subsequent stroke

Ann Neurol

Stroke and cancer: the importance of cancer-associated hypercoagulation as a possible stroke etiology

Stroke

Poor short-term outcome in patients with ischaemic stroke and active cancer

J Neurol

Intravenous thrombolysis in acute ischemic stroke with active cancer

Biomed Res Int

Endovascular thrombectomy for ischemic stroke increases disability-free survival, quality of life, and life expectancy and reduces cost

Front Neurol

Cost-effectiveness of thrombectomy in patients with acute ischemic stroke: the THRACE randomized controlled trial

Stroke